RGD Reference Report - Effect of suvorexant on morphine tolerance and dependence in mice: Role of NMDA, AMPA, ERK and CREB proteins. - Rat Genome Database

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Effect of suvorexant on morphine tolerance and dependence in mice: Role of NMDA, AMPA, ERK and CREB proteins.

Authors: Esmaili-Shahzade-Ali-Akbari, Peyman  Hosseinzadeh, Hossein  Mehri, Soghra 
Citation: Esmaili-Shahzade-Ali-Akbari P, etal., Neurotoxicology. 2021 May;84:64-72. doi: 10.1016/j.neuro.2021.02.005. Epub 2021 Feb 18.
RGD ID: 401940121
Pubmed: PMID:33609567   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuro.2021.02.005   (Journal Full-text)

The major problems of morphine use in the clinic are its tolerance and dependence. This study aimed to investigate the effect of suvorexant, a dual orexin receptor antagonist, on morphine-induced dependence and tolerance in mice and evaluate the level of NMDA, AMPA, ERK, p-ERK, CREB and p-CREB proteins in the brain. Tolerance and dependence were induced by repeated injection of morphine in mice (three times a day for 3 days, 50, 50, and 75 mg/kg /day). To evaluate the effects of the drugs on morphine-induced tolerance and dependence, suvorexant (30, 60 and 90 mg/kg), clonidine (positive control, 0.1 mg/kg) and saline were injected intraperitoneally 30 min before each injection of morphine. Tolerance and locomotor activity were assessed by tail-flick and open-field tests, respectively. The effect of suvorexant on the naloxone (5 mg/kg, ip)-induced morphine withdrawal, was also evaluated. Finally, the expression of proteins in the brain of mice was measured by western blot. Administration of suvorexant with morphine significantly reduced morphine-induced tolerance. Also, suvorexant attenuated the naloxone-precipitated opioid withdrawal. Suvorexant decreased morphine-enhanced levels of CREB and p-ERK proteins but did not affect the expression of NMDA and AMPA proteins compared to the morphine group. Suvorexant reduced morphine-induced tolerance and dependence through the inhibition of orexin receptors as well as changes in CREB and p-ERK protein levels in the brain.



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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
CREB1Humanmorphine dependence treatmentISOCreb1 (Mus musculus) RGD 
Creb1Ratmorphine dependence treatmentISOCreb1 (Mus musculus) RGD 
Creb1Mousemorphine dependence treatmentIEP  RGD 
MAPK1Humanmorphine dependence treatmentISOMapk1 (Mus musculus) RGD 
MAPK3Humanmorphine dependence treatmentISOMapk3 (Mus musculus) RGD 
Mapk1Ratmorphine dependence treatmentISOMapk1 (Mus musculus) RGD 
Mapk1Mousemorphine dependence treatmentIDA  RGD 
Mapk3Ratmorphine dependence treatmentISOMapk3 (Mus musculus) RGD 
Mapk3Mousemorphine dependence treatmentIDA  RGD 
1 to 9 of 9 rows


Genes (Rattus norvegicus)
Creb1  (cAMP responsive element binding protein 1) Mapk1  (mitogen activated protein kinase 1) Mapk3  (mitogen activated protein kinase 3)

Genes (Mus musculus)
Creb1  (cAMP responsive element binding protein 1) Mapk1  (mitogen-activated protein kinase 1) Mapk3  (mitogen-activated protein kinase 3)

Genes (Homo sapiens)
CREB1  (cAMP responsive element binding protein 1) MAPK1  (mitogen-activated protein kinase 1) MAPK3  (mitogen-activated protein kinase 3)